ABSTRACT Epidermal growth factor receptor (EGFR) inhibitors comprise a commonly prescribed class of drug that improves survival in patients with a variety of malignancies. Rash, particularly on the face, is the most common adverse event and occurs in 50-90% of patients, is severe in 10-20% of patients, lacks effective palliative options, and sometimes requires stopping cancer therapy. We have published qualitative research from patients who developed this rash and learned that it leads to cutaneous pain, psychological distress, and social isolation. One patient stated, My face looks so bad that if I go see my friends, they say, 'What happened to you.' I am self-conscious about that. Another commented, ?I just told them they would be better off just calling me, don't come visit.? Another described, I can feel the itch and burn all over. Some investigators have suggested that African American patients do not suffer these symptoms. Here, we hypothesize that they do, that their pigmented skin might camoflage the rash, but that this rash still causes them physical and psychological pain. Building on our data (a 933-patient epidemiologic study that shows rash is worse in men; pilot clinical trial data that show benefit with a topical anti-androgen; and an androgen-dependent gene profile from skin biopsies from patients with EGFR inhibitor rash) and on data from others (some melanocytes overexpress androgens and androgen receptors), we hypothesize this rash is androgen-driven and that the topical antiandrogen, ketoconazole, palliates it in all patients, including African American cancer patients. In Aim #1, we will interview African American patients who have developed this rash and will use novel qualitative methods to probe into their hypothesized psychological and cutaneous distress. In Aim #2, we will conduct a randomized, double-blinded, placebo-controlled trial with ketoconazole (a topical anti- androgen) to determine whether this agent palliates rash within a racially diverse cohort and to explore whether it does so by modulating androgen-dependent genes, as alluded to above. The long-term goal of this line of investigation is to reduce suffering and improve the quality of life of all patients -- including African American patients -- who suffer from EGFR inhibitor-induced rash.